摘要
为探讨表没食子儿茶素没食子酸酯(EGCG)对阿尔茨海默症(Alzheimer's disease,AD)模型动物认知功能缺陷、海马神经发生和突触功能损伤影响,6月龄APP/PS1双转基因小鼠和C57小鼠分别给予EGCG(20mg.kg-1.d-1)或生理盐水腹腔注射,连续给药5周。利用Morris水迷宫试验和新物体识别试验检测EGCG对AD模型小鼠空间学习记忆能力影响,免疫组织化学方法检测EGCG对AD模型小鼠海马新生神经干细胞数量、新生神经元数量以及突触密度影响。Morris水迷宫结果显示,EGCG能显著缩短AD模型小鼠逃避潜伏期和游泳路径,并显著增加其跨越平台次数(P<0.01)。新物体识别试验结果显示,EGCG能够显著增加AD模型小鼠新物体识别指数(P<0.05)。免疫组化结果显示,EGCG能够显著增加AD模型小鼠海马齿状回区域新生神经干细胞数量和新生神经元数量(P<0.01),同时EGCG也显著增加AD模型小鼠海马CA1区域突触密度(P<0.01)。表明EGCG可以促进AD模型小鼠海马神经发生、提高突触密度,从而提高学习记忆能力,为EGCG用于临床治疗AD及痴呆患者提供新分子机制和理论依据。
To investigate the effect of Epigallocatechin-3-Gallate （EGCG） on cognitive dysfunction, impaired hippocampal neurogenesis and synaptic function in Alzheimer＇s disease（AD） model mice, 6-month-old APP/PS1 double transgenic mice and age-matched wild-type C57 mice were divided into two groups and intraperitoneally injected with either EGCG （20 mg- kg-1. d-1） or saline, once dairy for 5 weeks. The effect of EGCG on leaming and memory in AD mice was examined by Morris water maze task （MWM） and novel object recognition tasks （NOR）. The effect of EGCG on hippocampal neurogenesis and synaptic density was assessed by immunofluorescence staining. In the MWM test, EGCG-injected AD mice displayed shorter escape latencies and swimming path to find the platform position and more times crossing the hidden platform as compared to saline-injected AD mice （P〈0.01）. Likewise, EGCG treatment significantly increased the novel object recognition index in AD mice （P〈0.05）. Following EGCG treatment, the number of newbornneural stem cells and immature neurons in the dentate gyrus of the hippocampus increased dramatically in AD mice （P〈0.01）. Moreover, EGCG obviously increased the synaptic density of CA1 in the hippocampus in AD mice （P〈0.01）. These results suggested that EGCG promoted hippocampal neurogenesis, increased synaptic density and ameliorated the cognitive deficits in AD mice, which had provided a theoretical basis for the application of EGCG in AD treatment.
出处
《东北农业大学学报》
CAS
CSCD
北大核心
2013年第6期80-85,F0003,共7页
Journal of Northeast Agricultural University
基金
生物膜与膜生物工程国家重点实验室基金
清华裕元医学科学研究基金(20240000514)
